Toxicological evaluation of the hydroethanol extract of Tabernaemontana crassa (Apocynaceae) stem bark

Aim

Tabernaemontana crassa Benth. is a medicinal plant widely used in Cameroon folk medicine to treat a variety of affections. This study was aimed at evaluating its toxicological profile.

Materials and methods

The 70% (v/v) hydroethanol (HE) extract from the stem bark of this plant was given to albino Wistar rats by oral gavage to study the acute and sub-acute toxicities.

Results

The results of histopathological studies revealed that there was a dose-related effect in liver, lungs and kidneys and that there was no difference in tissue profile of control group and those receiving 6 weeks daily treatment of 0.5 g/kg b.w. The result of the acute toxicity indicated the medium lethal dose (LD50) of 6.75 g/kg body weight (b.w.) after 48 h of treatment and the significant variation (P < 0.05) of the relative body weight, serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), total bilirubin (TBil), direct bilirubin (DBil) and creatinine (SCr) at the dose of 6 g/kg b.w. These results also indicated significant variation of the liver alkaline phosphatase, aspartate aminotransferase (AST), ALT, total proteins (TP), glutathione (GSH) and malondialdehyde (MDA) and renal creatinine (RCr) and urea (RU) at 6 g/kg b.w. The result of the sub-acute toxicity showed significant changes in the body weight but no modification (P > 0.05) of blood and liver indices for the animal taking 6 weeks daily doses of the HE compared to the control group.

Conclusions

The results showed that this extract was fairly non-toxic but that consumption of higher doses up to 6 g/kg b.w. could cause organ injuries. Moderated consumption of small doses up to 0.5 g/kg b.w. daily for 6 weeks appeared to be safe.     

Hepatoprotective activity of Phyllanthus amarus Schum. et. Thonn. extract in ethanol treated rats: in vitro and in vivo studies

The present study was undertaken to investigate the protective effect and possible mechanism of aqueous extract from Phyllanthus amarus Schum. et. Thonn. (PA) on ethanol-induced rat hepatic injury. In the in vitro study, PA (1-4 mg/ml) increased %MTT reduction assay and decreased the release of transaminases (AST and ALT) in rat primary cultured hepatocytes being treated with ethanol. Hepatotoxic parameters studied in vivo included serum transaminases (AST and ALT), serum triglyceride (STG), hepatic triglyceride (HTG), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta), together with histopathological examination. In acute toxicity study, single dose of PA (25, 50 and 75 mg/kg, p.o.) or SL (silymarin, a reference hepatoprotective agent, 5 mg/kg), 24h before ethanol (5 g/kg, p.o.) lowered the ethanol-induced levels of transaminases (AST and/or ALT). The 75 mg/kg PA dose gave the best result similar to SL. Treatment of rats with PA (75 mg/(kg day), p.o.) or SL (5 g/(kg day), p.o.) for 7 days after 21 days with ethanol (4 g/(kg day), p.o.) enhanced liver cell recovery by bringing the levels of AST, ALT, HTG and TNF-alpha back to normal. Histopathological observations confirmed the beneficial roles of PA and SL against ethanol-induced liver injury in rats. Possible mechanism may involve their antioxidant activity.     

Antroquinonol from ethanolic extract of mycelium of Antrodia cinnamomea protects hepatic cells from ethanol-induced oxidative stress through Nrf-2 activation

Aim of the study

In recent years, the medicinal mushroom Antrodia cinnamomea, known as “niu-chang chih” has received much attention with regard to its possible health benefits; especially its hepatoprotective effects against various drugs, toxins, and alcohol induced liver diseases. However, the molecular mechanism underlying this protective effect of Antrodia cinnamomea and its active compound antroquinonol was poorly understood. In the present study we evaluated to understand the hepatoprotective efficacy of antroquinonol and ethanolic extracts of mycelia of Antrodia cinnamomea (EMAC) in vitro and in vivo.

Materials and methods

The protective mechanism of antroquinonol and EMAC against ethanol-induced oxidative stress was investigated in cultured human hepatoma HepG2 cells and ICR mice model, respectively. HepG2 cells were pretreated with antroquinonol (1-20 μM) and oxidative stress was induced by ethanol (100 mM). Meanwhile, male ICR mice were pretreated with EMAC for 10 days and hepatotoxicity was generated by the addition of ethanol (5 g/kg). Hepatic enzymes, cytokines and chemokines were determined using commercially available assay kits. Western blotting and real-time PCR were subjected to analyze HO-1 and Nr-2 expression. EMSA was performed to monitor Nrf-2 ARE binding activity. Possible changes in hepatic lesion were observed using histopathological analysis.

Results

Antroquinonol pretreatment significantly inhibited ethanol-induced AST, ALT, ROS, NO, MDA production and GSH depletion in HepG2 cells. Western blot and RT-PCR analysis showed that antroquinonol enhanced Nrf-2 activation and its downstream antioxidant gene HO-1 via MAPK pathway. This mechanism was then confirmed in vivo in an acute ethanol intoxicated mouse model: serum ALT and AST production, hepatocellular lipid peroxidation and GSH depletion was prevented by EMAC in a dose-dependent manner. EMAC significantly enhanced HO-1 and Nrf-2 activation via MAPKs consistent with in vitro studies. Ethanol-induced hepatic swelling and hydropic degeneration of hepatocytes was significantly inhibited by EMAC in a dose-dependent manner.

Conclusions

These results provide a scientific basis for the hepatoprotective effects of Antrodia cinnamomea. Data also imply that antroquinonol, a potent bioactive compound may be responsible for the hepatoprotective activity of Antrodia cinnamomea. Moreover, the present study highly supported our traditional knowledge that Antrodia cinnamomea as a potential candidate for the treatment of alcoholic liver diseases.     

茵栀黄颗粒的保肝作用研究

目的：研究茵栀黄颗粒的保肝作用。方法：采用D-氨基半乳糖(D-GaIN)、四氯化碳(CCl4)造成急性肝损伤,以血清ALT与AST、肝组织病变程序为指标,并以茵栀黄颗粒口服液为阳性对照,观察茵栀黄颗粒的药效。另外,给小鼠ig异硫氰酸-1-奈脂,以血清胆红素为指标,观察茵栀黄颗粒的作用。结果：1．8g／kg、3．6g／kg茵栀黄颗粒组均能降低D-GaIN所致的小鼠血清ALT、AST升高,3．6g／kg茵栀黄颗粒组还能减轻肝组织病变程度。1．0g／kg、2．0异／kg茵栀黄颗粒组均能降低CCl4所致的大鼠血清ALT、AST升高,2．0g／kg茵栀黄颗粒组还能减轻肝组织病变程度。1．8g／kg、3．6g／kg茵栀黄颗粒组均能降低异硫氰酸-1-奈脂所致总胆红素和结合胆红素升高。结论：茵栀黄颗粒对D-GaIN、CCl4所致的急性肝损伤均有明显的保护作用,对异硫氰酸-1-奈脂所致小鼠血清高胆红素有明显的降低作用。     

Hepatoprotective and anti-inflammatory activities of Ballota glandulosissima

Water extract of Ballota glandulosissima Hub.-Mor & Patzak (Lamiaceae) (BG) was investigated for anti-inflammatory activity using the carrageenan-induced rat paw oedema test and for hepatoprotective effect on carbon tetrachloride (CCl(4))-induced hepatotoxicity in rats. Biochemical parameters of hepatic damage such as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin concentrations were determined. CCl(4) (0.8 mL/kg i.p. for 7 days) treatment increased the serum AST, ALT, ALP and bilirubin levels significantly as compared to controls. Treatment of animals with BG (100 mg/kg, i.p.) +CCl(4) (0.8 mL/kg i.p.) for 7 days significantly ameliorated the levels of AST, ALT and ALP elevated by the CCl(4) treatment alone. The results of biochemical tests were also confirmed by histopathological examination. BG together with CCl(4) treatment decreased the balloning degeneration but did not produced apoptosis of hepatocytes, centrilobular and bridging necrosis observed in the CCl(4) treatment alone. BG, at 100 mg/kg per os, showed a significant reduction (34.22%) in rat paw oedema induced by carrageenan. The reference anti-inflammatory drugs etodolac (50 mg/kg, p.o.) and indomethacin (3 mg/kg, i.p.) significantly reduced the oedeme by 43.42 and 95.70%, respectively. The present study reveals that the water extract of Ballota glandulosissima possesses promising protective activity against CCl(4) induced hepatic damage and anti-inflammatory activity in rats.     

The adjuvant effects of Antrodia Camphorata extracts combined with anti-tumor agents on multidrug resistant human hepatoma cells

AIM OF THE STUDY: The objectives of this study were to investigate the adjuvant anti-tumor effects of Antrodia camphorate in human hepatoma cells (C3A and PLC/PRF/5) which are resistance to most anti-tumor agents, elucidate the possible regulation pathways, and measure the tumor growth and survival rate in xenograft-nude mice after combined with anti-tumor agents. MATERIALS AND METHODS: The AC extracts were measured by using a phenol/sulfuric acid method as previously described. The in vitro cell proliferation assay of ACs and anti-tumor agents was tested on C3A and PLC/PRF/5 cell lines. The percentage of human hepatoma cells undergoing apoptosis and distributing in different phases of cell cycle were determined by Flow cytometric analysis. Western blot analysis for MDR-1 and apoptosis- related proteins. The measurements of tumor growth and survival analysis of hepatoma implanted nude mice treated with Antrodia camphorata extracts and anti-tumor agents alone or in combinations. RESULTS: We have found that Antrodia camphorata extracts, when combined with anti-tumor agents, showed adjuvant antiproliferative effects on hepatoma cells (in vitro) and on xenografted cells in tumor-implanted nude mice (in vivo), which then extended their median survival days. Furthermore, solid-state extracts of Antrodia camphorata (AC-SS) showed its adjuvant effects through the inhibition of MDR gene expressions and the pathway of COX-2- dependent inhibition of p-AKT, which ultimately resulted in the induction of apoptosis in hepatoma cells. CONCLUSIONS: In this study, we have found that Antrodia camphorata extract, when combined with anti-tumor agents, showed adjuvant antiproliferative effects on hepatoma cells (in vitro) and on xenografted cells in tumor-implanted nude mice (in vivo).     

In vitro and in vivo hepatoprotective and antioxidant activity of ethanolic extract from Meconopsis integrifolia (Maxim.) Franch

Ethnopharmacological relevance

Meconopsis integrifolia (Maxim.) Franch is a high mountain endemic species used as a traditional Tibetan and Mongolian herb to treat hepatitis, pneumonia, and edema. This study aims to investigate the hepatoprotective and antioxidant effects of Meconopsis integrifolia ethanolic extract (MIE) in vitro and in vivo.

Materials and methods

The in vitro antioxidant property of MIE was investigated by employing various established systems. Rats with carbon tetrachloride (CCl₄)-induced liver injury were used to assess the hepatoprotective and antioxidant effect of MIE in vivo. The level or activity of alkaline phosphatase (ALP), glutamate pyruvate transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) in the blood serum and thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in the liver and kidney of the rats were assayed using standard procedures.

Results

MIE exhibited strong antioxidant ability in vitro. In the rats with CCl₄-induced liver injury, the groups treated with MIE and silymarin showed significantly lower levels of ALT, AST, ALP, and TB. MIE demonstrated good antioxidant activities in both the liver and kidney of the rats in vivo.

Conclusions

MIE exhibits excellent hepatoprotective effects and antioxidant activities in vitro and in vivo, supporting the traditional use of Meconopsis integrifolia in the treatment of hepatitis.     

Antihepatotoxic activity of a quantified Desmodium adscendens decoction and d-pinitol against chemically-induced liver damage in rats

Ethnopharmacological relevance

The isolation of d-pinitol (or 3-O-methyl-d-chiro-inositol) from an aqueous decoction of Desmodium adscendens (Fabaceae) leaves and twigs is reported. The protective and curative effect of this decoction, in which d-pinitol was quantified, and of pure d-pinitol, against chemically-induced liver damage in rats has been evaluated.

Materials and methods

Enzyme levels of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP), which are among the usual biomarkers for liver damage, were determined in serum samples of experimental animals. The protective effects against d-galactosamine-induced and ethanol-induced liver damage of a decoction of D. adscendens, quantified on its main constituent d-pinitol, was investigated in rats. In addition, the curative effects of pure d-pinitol and D. adscendens against chronic d-galactosamine-induced and acute acetaminophen-induced hepatotoxicity in rats was studied. Silymarin was used as positive control.

Results

In a first experiment evaluating the protective effect against acute d-galactosamine-induced liver damage in rats, a significant decrease of AST and ALT was observed for the D. adscendens decoction at a dose equivalent to 5 mg/kg/day and 20 mg/kg/day d-pinitol, as well as 20 mg/kg/day pure d-pinitol. With respect to chronic ethanol-induced liver damage in rats, the protective effects of D. adscendens at doses equivalent to 2 mg/kg/day and 10 mg/kg/day d-pinitol, were not observed for serum AST and ALT levels. However, with respect to reduced mortality of animals, statistical analysis showed a trend towards significance for the Desmodium group receiving a dose equivalent to 10 mg/kg/day d-pinitol, versus the untreated hepatotoxic animals. Additional experiments in rat models of acute acetaminophen-induced and chronic d-galactosamine-induced liver damage indicated that D. adscendens decoction and pure d-pinitol had no curative effect when given in a dose equivalent to 10 mg/kg/day d-pinitol, or up to 20 mg/kg/day as a pure compound daily, respectively.

Conclusions

The aqueous decoction of D. adscendens showed a protective effect in rats against liver damage induced by d-galactosamine and ethanol, and this effect is at least in part due to the presence of d-pinitol. However, no curative effect of D. adscendens decoction or d-pinitol on liver damage induced by the tested chemicals could be demonstrated.     

亮菌多糖ATPS-2对小鼠免疫性肝损伤的保护作用

目的：观察亮菌多糖ATPS-2对卡介苗加脂多糖(BCG＋LPS)引起的小鼠免疫性肝损伤的影响。方法：建立BCG+LPS致小鼠免疫性肝损伤模型,比色法测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和一氧化氮(NO)的水平,肝脏中超氧化物歧化酶(SOD)活力、丙二醛(MDA)浓度,酶联免疫法测定血清TNF-α,IL-1的含量,用MTT法测定脾T,B淋巴细胞增殖能力,分别计算各组肝脏指数、脾脏指数和胸腺指数。结果：亮菌多糖ATPS-2(25,50,100 mg·kg^-1)能明显降低小鼠血清中升高的ALT,AST,NO水平以及TNF-α,IL-1的含量,抑制肝脏中上升的MDA水平和提高过低的SOD活性,各用药组均能提升脾T,B淋巴细胞增殖能力,且均不同程度地提高了小鼠的脾脏指数和胸腺指数,降低了小鼠的肝脏指数。结论：亮菌多糖ATPS-2对BCG＋LPS致小鼠免疫性肝损伤具有显著的保护作用。     

维药菊苣对小鼠急性化学性肝损伤的保护作用

目的:观察菊苣乙醇提取物和水提物对四氯化碳所致小鼠急性肝损伤的保护作用。方法:用95%乙醇和蒸馏水对药材进行回流提取,用0.1%四氯化碳橄榄油溶液10m l/kg腹腔注射造模,以血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)含量为指标观察对肝损伤的保护作用。结果:菊苣水提物(1.5g/kg、3g/kg、6g/kg)、醇提物(1.6g/kg、3.2g/kg、6.4g/kg)对CC l4所致肝损伤小鼠血清升高的ALT、AST有降低作用。结论:菊苣水提物和乙醇提取物对小鼠四氯化碳所致小鼠急性肝损伤有保护作用。     

The protective effects of Phyllanthus emblica Linn. extract on ethanol induced rat hepatic injury

This study was undertaken to investigate the protective effects of Phyllanthus emblica Linn. (PE) extract on ethanol induced rat hepatic injury. PE (0.5 and 1 mg/ml) increased cell viability of rat primary cultured hepatocytes being treated with ethanol (96 microl/m) by increasing % MTT and decreasing the release of transaminase. Hepatotoxic markers studied in rats included serum transaminases (AST and ALT), serum triglyceride (STG), hepatic triglyceride (HTG), TNF-alpha and IL-1beta together with histopathological examination. Pretreatment of rats with PE at oral dose of 25, 50 and 75 mg/kg or SL (silymarin, a reference hepatoprotective agent) at 5 mg/kg, 4 h before ethanol, lowered the ethanol induced levels of AST, ALT and IL-1beta. The 75 mg/kg PE dose gave the best result similar to SL. Treatment of rats with PE (75 mg/kg/day) or SL (5 mg/kg/day) for 7 days after 21 days with ethanol (4 g/kg/day, p.o.) enhanced liver cell recovery by bringing the levels of AST, ALT, IL-1beta back to normal. Histopathological studies confirmed the beneficial roles of PE and SL against ethanol induced liver injury in rats.     

Inhibition of chemically induced inflammation and pain by orally and topically administered leaf extract of Manihot esculenta Crantz in rodents

The aqueous leaf extract of Manihot esculenta Crantz (MELE) is being used orally and topically in traditional African medicine for the treatment of inflammation and pain, and claimed to be safe. The anti-inflammatory effects of MELE (100-400mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) were tested against carrageenan-induced paw oedema in rats as well as against xylene-induced ear oedema in mice. The analgesic effect of MELE (100-400mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) was tested against acetic acid-induced (20mul, 0.6%, v/v in normal saline, i.p.) and acetylcholine-induced (8.3mg/kg, i.p.) mouse writhing models. At 100-400mg/kg, p.o. and 1-4% (w/w), topically, MELE produced significant inhibitions of carrageenan-induced rat paw oedema and xylene-induced ear swelling in mice. Effects produced by MELE were significantly higher than those produced by indomethacin (10mg/kg, s.c. or 1%, w/w in petroleum jelly) in the anti-inflammatory models. For the analgesic effect, MELE (100-400mg/kg, orally) and (1-4%, w/w, topically), like aspirin (100mg/kg, i.p.) exhibited significant (P<0.05) inhibition of acetic acid- and acetylcholine-induced mouse writhing tests, compared to untreated control. Effects produced by MELE were significantly lower than those produced by aspirin (100mg/kg, i.p.) in the analgesic models, except for the topically administered extract on acetylcholine-induced pain. Acute oral administration up to 10g/kg did not cause death within 14 days, but mortalities were produced in i.p. administered extract with LD(50) of 2.5+/-0.3g/kg. Based on these, the extract may contain orally safe, topically and orally effective anti-inflammatory and analgesic principles, which justify its use in traditional African medicine.     

Hepatoprotective and antioxidant effects of the methanolic extract from Halenia elliptica

Aims of study

Halenia elliptica, a medicinal herb of Tibetan origin, was commonly used in folk medicine to treat hepatitis. The aim of the present study is to evaluate the hepatoprotective and antioxidant activity of Halenia elliptica against experimentally induced liver injury.

Materials and methods

The antioxidant property of methanolic extract (ME) of Halenia elliptica was investigated by employing various established in vitro systems. The ME of Halenia elliptica was studied here for its hepatoprotective effects against CCl₄-induced liver toxicity in rats. Activity was measured by monitoring the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin.

Results

The ME possessed strong antioxidant activity in vitro. The results of CCl₄-induced liver toxicity experiment showed that rats treated with the ME of Halenia elliptica (100 mg/kg and 200 mg/kg), and also the standard treatment, silymarin (50 mg/kg), showed a significant decrease in ALT, AST, ALP, and total bilirubin levels, which were all elevated in the CCl₄ group (p < 0.01). The results observed after administration of 100 mg/kg ME were comparable to those of silymarin at 50 mg/kg (p > 0.05). The ME did not show any mortality at doses up to 2000 g/kg body weight.

Conclusion

These results seem to support the traditional use of Halenia elliptica in pathologies involving hepatotoxicity, and the possible mechanism of this activity may be due to strong free radical-scavenging and antioxidant activities of ME.     

高山红景天对对乙酰氨基酚所致小鼠急性肝损伤的保护作用

目的观察高山红景天(Rhodiola sachalinesis A.Bor)对对乙酰氨基酚(Acetaminophen.AAP)所致小鼠急性肝损伤的保护作用。方法用红景天醇提物或红景天水提物1 g/kg给小鼠灌胃1 h后,灌1 g/kg的对乙酰氨基酚,观察小鼠死亡率的变化;提前1 h用不同剂量的红景天醇提物或红景天水提物处理后,再灌0.5 g/kg的对乙酰氨基酚,以血清中天冬氨酸氨基转移酶(AST/GOT),丙氨酸氨基转移酶(ALT/GPT),观察红景天醇提物及红景天水提物对肝损伤的保护作用[1]。结果给小鼠对乙酰氨基酚1 g/kg灌胃组,24 h后可致80%小鼠死亡;提前1 h用红景天醇提物及红景天水提物灌胃其死亡率可分别下降至30%和20%,而且能不同程度降低血清中AST,ALT的含量,与水飞蓟素无明显差别。结论红景天醇提物及红景天水提物对对乙酰氨基酚所致小鼠急性肝损伤有一定保护作用。     

Antioxidant activity of Antrodia camphorata on free radical-induced endothelial cell damage

AIM OF THE STUDY: Antrodia camphorata (A. camphorata) is well known in Taiwan as a traditional Chinese medicine. The purpose of this study is to evaluate the antioxidant activity of Antrodia camphorata on free radical-induced endothelial cell damage. MATERIALS AND METHODS: In this study, a human umbilical vein endothelial cell (EC) culture system was used to evaluate the effects of the fermented culture broth of A. camphorata (FCBA) and aqueous extracts of mycelia from A. camphorata (AEMA) against the oxidative cell damage induced by the free-radical generator AAPH. RESULTS: The present investigations show that FCBA (25-100 microg/mL) and AEMA (50-200 microg/mL) effectively protect the ECs from damage after exposure to 15 mM AAPH for 16h. However, cell viability was not affected in ECs under controlled conditions after FCBA or AEMA treatment. An increase in EC prostacyclin (PGI(2)) production in response to AAPH exposure was positively and negatively correlated with cell damage and FCBA/AEMA concentration, respectively. Both FCBA and AEMA treatment significantly inhibited AAPH-apoptotic cell death in the ECs, as evidence by reduced DNA fragmentation, cytochrome c release, caspase-3 activation, and dysregulation of Bcl-2 and Bax. Moreover, the AAPH-induced reductions in EC SOD activity and protein levels are prevented by FCBA and AEMA. CONCLUSION: Our findings suggest that A. camphorata possesses antioxidant properties and improves endothelial function, further offering effective protection from atherosclerosis.     

Antioxidant and hepatoprotective activity of Fagonia schweinfurthii (Hadidi) Hadidi extract in carbon tetrachloride induced hepatotoxicity in HepG2 cell line and rats

Ethnopharmacological relevance

The whole plant of Fagonia schweinfurthii (Hadidi) Hadidi (Family: Zygophyllaceae) is used in variety of diseases including hepatic ailments in deserts and dry areas of India.

Aim of the study

To evaluate antioxidant and hepatoprotective activity of ethanolic extract from Fagonia schweinfurthii (Hadidi) Hadidi (FSEE) in carbon tetrachloride (CCl₄) induced hepatotoxicity in HepG2 cell line and rats.

Materials and methods

In vitro antioxidant activity was determined by DPPH, ABTS radicals and hydrogen peroxide methods. In vitro cytotoxicity and hepatoprotective potential of FSEE were evaluated using HepG2 cells. Based on the cytotoxicity assay, FSEE (50, 100, 200 µg/ml) was assessed for hepatoprotective potential against CCl₄ induced toxicity in HepG2 cell line by monitoring cell viability, aspartate aminotransferase (AST), alanine aminotransaminase (ALT), lactate dehydrogenase (LDH) leakage, lipid peroxidation (LPO) and glutathione level (GSH). Further, in vivo hepatoprotective activity of FSEE was evaluated against CCl₄ induced hepatotoxicity in male Wistar albino rats. Rats were pre-treated with FSEE (200 mg, 400 mg kg⁻¹ day⁻¹ p.o.) for 7 days followed by a single dose of CCl₄ (1.0 ml/kg, i.p.) on 8th day. Silymarin was used as positive control. After 24 h of CCl₄ administration, various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB) and total protein (TP) levels were estimated in serum. The antioxidant parameters like superoxide dismutase (SOD) activity, catalase (CAT) activity, glutathione (GSH) content and malondialdehyde (MDA) level in the liver homogenate were determined. Histopathological changes in the liver of different groups were also studied.

Results

The FSEE possessed strong antioxidant activity in vitro. The results indicated that CCl₄ treatment caused a significant decrease in cell viability. The CCl₄-induced changes in the HepG2 cells were significantly ameliorated by treatment of the FSEE. FSEE significantly prevented CCl₄ induced elevation of AST, ALT, ALP, TB, and CCl₄ induced decrease in total protein in rats. FSEE treated rat liver anti-oxidant parameters (SOD, CAT, MDA and GSH,) were significantly antagonized for the pro-oxidant effect of CCl₄. Histopathological studies also supported the protective effect of FSEE.

Conclusion

The results of this study revealed that FSEE has significant hepatoprotective activity. This effect may be due to the ability of the extract to inhibit lipid peroxidation and increase in the anti-oxidant enzymatic activity.     

Acute and subchronic oral toxicity assessment of the aqueous extract from the stem bark of Erythrina senegalensis DC (Fabaceae) in rodents

Aim of the study

The decoction of the stem bark of Erythrina senegalensis (EAES) is traditionally used in the Western region of Cameroon against liver disorders. The present study evaluated the potential toxicity of this decoction after acute and sub-chronic administration in rodents.

Materials and methods

In acute study, a single administration of EAES was given orally to mice at doses ranging from 1.25 to 12.5 g/kg. General behaviour, adverse effects and mortality were determined for up to 14 days post treatment. In the sub-chronic study, EAES was given orally as a single administration to Wistar rats at doses of 300, 600 and 1200 mg/kg/day for 28 days. Animal body weight was observed throughout the experimental period while haematological and biochemical parameters of blood and urine, as well as kidney and liver tissues histology were evaluated at the end of the experiment.

Results

In the acute study in mice, none of the doses used induced mortality or significant behavioural changes. In the sub-chronic study in rats, daily oral administration of EAES at the dose of 600 mg/kg resulted in a significant increase in the relative body weight at the last week of treatment. The relative weights of organs were not affected by the treatment. No haematological changes were observed a part of a significant increase in WBC count at the dose of 600 mg/kg. Serum AST, ALT, ALP, total protein, total cholesterol and triglycerides decreased significantly while total and conjugated bilirubin significantly increased. Renal function indices assay in blood showed significant modification in all the treated groups compared to control while, in urine, only urea excretion markedly reduced at a dose of 1200 mg/kg. Histological analysis did no show any liver or kidney alteration.

Conclusion

These results demonstrated that there is a wide margin of safety for the therapeutic use of EAES and further corroborated the traditional use of this extract as a hepatoprotective agent.     

Hepatoprotective effect of Trichosanthes cucumerina Var cucumerina L. on carbon tetrachloride induced liver damage in rats

Ethnopharmacological relevance

Different parts of the plant Trichosanthes cucumerina Var cucumerina L. (cucurbitaceae) are used to treat liver disorders, traditionally. It is one among the constituents in various Ayurvedic formulations used for the treatment of liver disorders and other diseases.

Aims of study

The aim of the present study is to evaluate the protective effect of Trichosanthes cucumerina against experimentally induced liver injury.

Materials and methods

The methanolic extract of whole plant of Trichosanthes cucumerina (TCME) was evaluated for the hepatoprotective activity against carbon tetrachloride (CCl₄) induced hepatotoxicity in rats. Various biochemical parameters like alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), total protein (TP) and albumin (ALB) levels were estimated in serum as well as the glutathione (GSH) and malondialdehyde (MDA) levels in the liver were determined. Histopathological changes in the liver of different groups were also studied.

Results

The pre-treatment of TCME at dose levels of 250 and 500 mg/kg b.w.p.o. had controlled the raise of AST, ALT, ALP, TB and MDA levels and the effects were comparable with standard drug (silymarin 100 mg/kg b.w.p.o.). The GSH, TP and ALB levels were significantly increased in the animals received pre-treatment of the extract. The animals received pre-treatment of the extract shown decreased necrotic zones and hepatocellular degeneration when compared to the liver exposed to CCl₄ intoxication alone. Thus the histopathalogical studies also supported the protective effect of the extract.

Conclusion

This study demonstrates the hepatoprotective activity of Trichosanthes cucumerina and thus scientifically supports the usage of this plant in various Ayurvedic preparations and traditional medicine for treatment of liver disorders.